GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms.

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

UniProt:C5B1I4

UniProt entry for mllA siderophore synthetase component

Annotated as a siderophore synthetase component

"SubName: Full=Siderophore synthetase component"
Belongs to the IucA/IucC family

"SIMILARITY: Belongs to the IucA/IucC family"
Contains an aerobactin biosynthesis IucA/IucC N-terminal domain (residues 139-364)

"Aerobactin siderophore biosynthesis IucA/IucC N-"
Contains an aerobactin biosynthesis IucA/IucC-like C-terminal domain (residues 396-556)

"Aerobactin siderophore biosynthesis IucA/IucC-like"

PMID:39078674

Identification and characterization of a small-molecule metallophore involved in lanthanide metabolism

The mll cluster (META1p4129-4138) produces methylolanthanin, a lanthanophore

"the genes META1p4129 through META1p4138 were the most highly up-regulated in the Nd2O3 condition... The locus, which we have named mll (for methylolanthanin"
The mll cluster is highly upregulated in response to poorly bioavailable lanthanides

"META1p4129 through META1p4138 were the most highly up-regulated in the Nd2O3 condition, with an average increase in expression of 32-fold compared to growth with NdCl3"
mllA (META1p4132) is homologous to asbA-like NIS synthetase

"META1p4132-4135 (mllA, mllBC, mllDE, and mllF) are homologous to the well-studied petrobactin locus in B. subtilis, asbABCDEF"
Deletion of the mll cluster decreases lanthanide bioaccumulation

"production of methylolanthanin is required for normal levels of Ln accumulation... while overexpression of the molecule greatly increases bioaccumulation and adsorption"

file:METEA/mllA/mllA-deep-research-falcon.md

Falcon deep research report on mllA

mllA (META1p4132) maps to the methylolanthanin (mll) biosynthetic gene cluster; Zytnick et al. list META1p4132-4135 as mllA, mllBC, mllDE, and mllF.

"META1p4132–4135 as"
Zytnick et al. explicitly establish that META1p4132 is mllA in M. extorquens AM1.

"META1p4132 is mllA"
IucA/IucC-family NIS synthetases are ATP-dependent ligases that form an amide bond between a carboxylate and an amine/hydroxamate via an acyl-adenylate (acyl-AMP) intermediate, releasing PPi then AMP.

"amide bond between a carboxylate and an amine/hydroxamate"
For IucA, kinetic and structural analyses support an ordered binding mechanism in which ATP binds first, then citrate, then the hydroxamate donor.

"ATP binds first, then citrate, then the hydroxamate donor"
Methylolanthanin is the first characterized biological lanthanide chelator (lanthanophore) and incorporates citrate plus amine-containing linkers, consistent with mllA acting as an ATP-dependent amide-forming enzyme.

"mllA functions as an ATP-dependent amide-forming enzyme"
The mll locus (META1p4129-4138) is highly induced (~32-fold) under poorly soluble Nd2O3 compared with soluble NdCl3, consistent with a role in mobilizing lanthanides when bioavailability is low.

"is highly induced (~32-fold) under Nd2O3"
mllA itself is most plausibly a cytosolic biosynthetic enzyme; the secreted methylolanthanin product chelates lanthanides extracellularly.

"likely cytosolic enzyme participating in biosynthesis of MLL"
Caveat - no accessible source provides a purified mllA enzyme assay; the reaction and substrate specificity of mllA are inferred from family mechanism, not directly demonstrated.

"none of the accessible sources provide a purified mllA enzyme assay specifying its exact substrates or catalytic step"
Pathway membership of mllA is experimentally supported at the cluster/product level, while enzyme-level chemistry remains inferred from family homology.

"pathway membership is experimentally supported, while enzyme-level chemistry remains inferred from family homology"

file:METEA/mllA/mllA-deep-research-cyberian.md

Deep research report on mllA from Cyberian AI

As a Type A NIS synthetase, MllA utilizes citrate as one of its substrates

"As a Type A NIS synthetase, MllA utilizes citrate as one of"
Inferred ordered sequential mechanism with ATP binding first, then citrate, then the modified amino acid nucleophile

"ATP binds first to the enzyme, followed by citrate, and finally the modified amino acid nucleophile"
The first partial reaction adenylates citrate to form a citryl-AMP intermediate

"The first partial reaction involves adenylation of citrate to form a citryl-AMP intermediate"

file:METEA/mllA/mllA-deep-research-perplexity.md

Deep research report on mllA from Perplexity AI

Methylolanthanin production supports lanthanide-dependent methylotrophy by delivering lanthanides to XoxF-type methanol dehydrogenase

"lanthanides are distributed to apoprotein forms of XoxF methanol dehydrogenase, enabling the enzyme to function and support methanol oxidation and methylotrophic growth"